Bonds created to-date by dentin adhesives are imperfect. Current methods of preventing bond degradation invariably leave a zone of resin-sparse, demineralized dentin which is susceptible to creep during function. These bonding methods also fail to address the issue of the existence of a porous adhesive resin layer with increased interfacial permeability which expedites hydrolysis of hydrophilic resin components. Clearly, a strategy that integrates contemporary biomineralization and nanotechnology concepts for remineralizing denuded collagen matrices within hybrid layers and depositing minerals to form nanocomposites within porous adhesive layers should be investigated as a more assertive means to improve the durability of resin-dentin bonds. Guided Tissue Remineralization, a biomimetic remineralization protocol using dual dentin matrix protein analogs in a bioactive, slow calcium release, phosphate-containing system has recently been reported by the Principal Investigator to induce intrafibrillar and interfibrillar remineralization of phosphoric acid-etched dentin. This research proposal investigates the application of Guided Tissue Remineralization to dentin bonding. The hypothesis that the Guided Tissue Remineralization approach can remineralize denuded collagen in poorly- infiltrated hybrid layers to the hierarchical apatite organization seen in natural mineralized intertubular dentin, and can form nanocomposites in porous adhesive layers of resin-dentin interfaces will be tested in Specific Aim 1. It is anticipated that the extent remineralization in hybrid layers will be highly variable, with poorly- infiltrated regions being highly remineralized and well-infiltrated regions sparsely remineralized. Thus, the hypothesis that intrafibrillar remineralization by Guided Tissue Remineralization improves the mechanical properties of the poorly-infiltrated regions beyond those exhibited by the non-remineralized, well-infiltrated regions of the hybrid layer will be tested in Specific Aim 2. The hypothesis that Guided Tissue Remineralization can remineralize imperfect bonds created in artificial carious dentin with much thicker zones of partially- demineralized dentin will further be tested using an artificial dentin caries model in Specific Aim 3. Collectively, the results should provide insight on the feasibility of a remineralization protocol that is based on non-classical crystallization pathways to remineralize resin-dentin interfaces in sound and artificial carious dentin. Research data acquired from this research proposal will form the foundation for more sophisticated translational strategies to be employed in a future R01 grant application for the development of Guided Tissue Remineralization-based delivery systems to extend the longevity of resin-dentin bonds. PUBLIC HEALTH RELEVANCE: This project investigates the use of contemporary biomineralization and nanotechnology concepts to improve the durability of resin-dentin bonds using a biomimetic analogs-containing remineralization medium that produces intrafibrillar and interfibrillar remineralization of resin-infiltrated demineralized dentin collagen matrices.